EP0197090A1 - Formation d'epiderme sur la surface d'un succedane dermique. - Google Patents

Formation d'epiderme sur la surface d'un succedane dermique.

Info

Publication number
EP0197090A1
EP0197090A1 EP85904951A EP85904951A EP0197090A1 EP 0197090 A1 EP0197090 A1 EP 0197090A1 EP 85904951 A EP85904951 A EP 85904951A EP 85904951 A EP85904951 A EP 85904951A EP 0197090 A1 EP0197090 A1 EP 0197090A1
Authority
EP
European Patent Office
Prior art keywords
equivalent
skin
dermal
cells
punch biopsies
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP85904951A
Other languages
German (de)
English (en)
Other versions
EP0197090B1 (fr
Inventor
Eugene Bell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Massachusetts Institute of Technology
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to AT85904951T priority Critical patent/ATE56620T1/de
Publication of EP0197090A1 publication Critical patent/EP0197090A1/fr
Application granted granted Critical
Publication of EP0197090B1 publication Critical patent/EP0197090B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005—The prosthesis being constructed from a particular material
    • A61F2310/00365—Proteins; Polypeptides; Degradation products thereof

Definitions

  • This invention is in the fields of biology and . 5 medicine and particularly relates to the . preparation of a living skin-equivalent which can be used to replace removed or damaged skin, particularly in human beings.
  • tissue-equivalents employing contractile agents incorporated into the lattices.
  • con ⁇ tractile agents include fibroblast cells and blood platelets .
  • the present invention is based upon the discov- 30 ery that skin-equivalent can be formed by modifying the procedures disclosed in Serial No. 381,978.
  • punch biopsies of skin are • incorporated into dermal-equivalent as a source of keratinocyte cells. It has now been found that such procedures result in excellent overgrowth of the dermal-equivalent by keratinocyte cells.
  • vSuch advantages include the fact that a differen- tiated epidermis can be formed in a relatively short period of time. Additionally, a small punch biopsy of skin, e.g. 2 millimeters, can be employed to cover a large area, e.g. 1 square centimeter (a 50 time amplification) . The area of a graft prepared by these techniques can be great because a number of punch biopsies can be inserted into a dermal- equivalent. Such punch biopsies can be inserted at the time that the dermal-equivalent is formed, or at a subsequent time.
  • Overgrowth of the punch biopsy is itself a selection process since only keratinocyte cells overgrow the dermal equivalent.
  • the overgrowth is free of dendritic cells.
  • the skin-equivalent formed by the use of punch biopsies may itself provide a source of material useful for production of additional skin-equiva ⁇ lents.
  • punch biopsies from a skin- equivalent may be employed in the production of other skin-equivalents.
  • stratum corneum that develops from skin-equivalents employing punch biopsies of skin is very similar to a normal stratum corneum.
  • the dermal/epidermal adherence • appears to be improved ' when punch biopsies of skin are employed compared to the previously employed plating techniques.
  • the punch biopsy method also accommodates well for application of other cells to the skin- equivalents.
  • pigment cells called melanocytes
  • melanocytes have been applied to the exposed surface of dermal-equivalent before they are over ⁇ grown with keratinocyte cells emanating from the punch biopsies.
  • melanocytes cover the melanocytes as they form a continuous layer of cells over the dermal equivalent.
  • the melanocytes become functional and contribute pigment to the keratinocyte layer.
  • the use of punch biopsies for epidermalizing the surface of dermal-equivalents also allows the immediate therapeutic clinical use of the skin- equivalents.
  • Dermal-equivalents can be cryopre-
  • the method is also very convenient for quantitative study of dermal/ epidermal interactions and for pharmacological testing.
  • Figure 1 is a photograph of a skin-equivalent prepared according to this invention
  • Figure 2 is a photograph illustrating applica ⁇ tion of a skin-equivalent according to this inven- * tion to a recipient.
  • the techniques of this invention are modifica ⁇ tions of the basic techniques employed in producing skin-equivalents by the methods described in Serial ⁇
  • Hydrated collagen lattices are prepared employ- ing collagen derived from rat tail tendon, calf skin collagen, or other sources. Solutions of collagen are prepared and maintained under slightly acidic conditions. Lattices are formed by adding fibro- blast cells, or other contractile agents, with nutrient medium and base which raises the pH suffi ⁇ ciently to induce fibrillogenesis and gel formation. Fibroblast cells, one example of a contractile agent, can be obtained from ⁇ man skin or from any human or animal tissue. A convenient technique for forming the lattice containing cells involves neutralizing an acidic collagen solution and rapidly combining it with cells and nutrient medium. Upon neutralization, collagen fibrils form and the lattice gels with fibroblast cells homogeneously dispersed therethrough.
  • the cells and collagen lattice are then maintained under conditions which allow the cells to attach to the * collagen lattice and to contract it to a fraction of its original size, thereby providing the dermal-equivalent.
  • Another contractile agent is blood platelets, which in many cases, can be obtained from the blood
  • Plate- lets are separated from whole blood by centrifuga- tion or other techniques for separating blood components from whole blood.
  • punch biopsies of skin can be obtained from the skin of a mouse, rat or human being, for example. These are typically obtained using cylindrical stainless steel punches which are typically in sizes of 2 or 4 mm in diameter. Punch biopsies are now routinely taken from human subjects for physio- pathological or therapeutic uses.
  • the skin biopsies taken with the punch can be incorporated into the dermal-equivalent lattice when it is poured.
  • the biopsy is positioned so that the epidermis can grow out at the level of -the upper surface of the dermal-equivalent.
  • the biopsy is held in place because the surrounding collagen lattice is con ⁇ tracted by the fibroblasts or other contractile agent. Inserting the biopsy at the * center of the dermal-equivalent results in radial outgrowth which-.- covers the dermal-equivalent. Outgrowth occurs as a circular sheet that consists of multiple layers of- .- keratinocyte cells. All phases of keratinocyte differentiation are represented in the epidermis, even close to the growing edge including a morpholo ⁇ gically normal stratum corneum. The granular layer of the differentiated epidermis contains membrane coating granules (Odlund granules) as observed in the epidermis, j ln vivo.
  • Keratinocyte cells from the primary biopsy have been subcultivated by taking punch biopsies from the skin-equivalent, i ⁇ i vitro. These starters of subcultures are handled in the same way as the original punch biopsies and are embedded in newly cast dermal-equivalents.
  • the rate of growth of epidermis from the punch is speeded up but an upshift to 1.5-2.0 x 10 ⁇ 3 M Ca +: is needed to simulate differentiation and keratinization.
  • FIG. 1 is a photograph of a skin-equivalent constituted with punch biopsies which serve as a source of keratinocyte cells that grow out and over the underlying dermal-equivalent.
  • the punch biop ⁇ sies were taken from a human donor. Each punch is surrounded by a halo that signifies the presence of a radially expanding epidermis.
  • Figure 2 is a photograph of a skin-equivalent being applied to a human patient1
  • the skin-equivalent described herein is suit- able for the treatment of a wound to the skin of a human being or other mammal. It is particularly suitable for treating massive burns and for treat ⁇ ment of a variety of genetic and other disorders that require skin replacement.

Abstract

Dans un procédé de préparation de succédanés dermiques vivants à partir de réseaux de collagène hydratés et contractés ayant des cellules kératinocytes à leur surface, des fragments de peau découpés et prélevés sont utilisés comme source de cellules kératinocytes pour les réseaux.
EP85904951A 1984-10-09 1985-10-04 Formation d'epiderme sur la surface d'un succedane dermique Expired - Lifetime EP0197090B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT85904951T ATE56620T1 (de) 1984-10-09 1985-10-04 Epidermalisierung der oberflaeche eines kuenstlichen dermas.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US658499 1984-10-09
US06/658,499 US4604346A (en) 1984-10-09 1984-10-09 Skin-equivalent prepared by the use of punch biopsy

Publications (2)

Publication Number Publication Date
EP0197090A1 true EP0197090A1 (fr) 1986-10-15
EP0197090B1 EP0197090B1 (fr) 1990-09-19

Family

ID=24641490

Family Applications (1)

Application Number Title Priority Date Filing Date
EP85904951A Expired - Lifetime EP0197090B1 (fr) 1984-10-09 1985-10-04 Formation d'epiderme sur la surface d'un succedane dermique

Country Status (5)

Country Link
US (1) US4604346A (fr)
EP (1) EP0197090B1 (fr)
JP (1) JPS62500435A (fr)
DE (1) DE3579810D1 (fr)
WO (1) WO1986002273A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6309454B1 (en) 2000-05-12 2001-10-30 Johnson & Johnson Medical Limited Freeze-dried composite materials and processes for the production thereof
EP1754513A2 (fr) 2005-08-17 2007-02-21 L'oreal Utilisation de l'acide 8-hexadécène-1,16-dicarboxylique comme agent de soin destiné à favoriser la cohésion de la couche cornée
WO2012059703A1 (fr) 2010-11-05 2012-05-10 Centre National De La Recherche Scientifique (Cnrs) Procede in vitro ou ex vivo pour la conservation et/ou la maintenance en survie d'un epiderme
WO2012163974A1 (fr) 2011-05-30 2012-12-06 L'oreal Modèle de cuir chevelu reconstruit, et traitement pour le criblage de molécules actives
WO2018020016A1 (fr) 2016-07-29 2018-02-01 L'oreal Équivalent de peau à compartiments dermiques juxtaposés distincts
WO2019063731A1 (fr) 2017-09-28 2019-04-04 L'oreal Signatures moléculaires de trois sous-populations de fibroblastes dermiques et équivalent dermique comprenant une de ces sous-populations
FR3111904A1 (fr) 2020-06-30 2021-12-31 L'oreal Bioencre pour bioimpression d’un modèle de jonction dermo-épidermique invaginée

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US5032508A (en) * 1988-09-08 1991-07-16 Marrow-Tech, Inc. Three-dimensional cell and tissue culture system
US5510254A (en) * 1986-04-18 1996-04-23 Advanced Tissue Sciences, Inc. Three dimensional cell and tissue culture system
US5266480A (en) * 1986-04-18 1993-11-30 Advanced Tissue Sciences, Inc. Three-dimensional skin culture system
US5160490A (en) * 1986-04-18 1992-11-03 Marrow-Tech Incorporated Three-dimensional cell and tissue culture apparatus
US5863531A (en) * 1986-04-18 1999-01-26 Advanced Tissue Sciences, Inc. In vitro preparation of tubular tissue structures by stromal cell culture on a three-dimensional framework
FR2612939B1 (fr) * 1987-03-26 1989-06-23 Cird Equivalent de peau
FR2612938B1 (fr) * 1987-03-26 1989-06-23 Cird Procede d'obtention d'un equivalent de peau et equivalent de peau correspondant
US4835102A (en) * 1987-03-31 1989-05-30 Eugene Bell Tissue equivalent test systems
US5273900A (en) * 1987-04-28 1993-12-28 The Regents Of The University Of California Method and apparatus for preparing composite skin replacement
US5108428A (en) * 1988-03-02 1992-04-28 Minnesota Mining And Manufacturing Company Corneal implants and manufacture and use thereof
AU4061989A (en) * 1988-08-04 1990-03-05 Carolyn C. Compton Transplanting cultured epithelial cells with a desired phenotypic trait
IL90690A0 (en) * 1988-09-30 1990-01-18 Organogenesis Inc Tissue equivalents and their preparation
US5106949A (en) * 1989-09-15 1992-04-21 Organogenesis, Inc. Collagen compositions and methods for preparation thereof
IL95429A (en) * 1989-09-15 1997-09-30 Organogenesis Living tissue equivalents comprising hydrated collagen lattice and a collagen gel and their production
US5292655A (en) * 1990-01-29 1994-03-08 Wille Jr John J Method for the formation of a histologically-complete skin substitute
HUT63319A (en) * 1990-04-24 1993-08-30 Mark Eisenberg Method for producing composition equivalent with living skin
IT1248934B (it) * 1990-06-01 1995-02-11 Fidia Spa Membrane forate biocompatibili,processi per la loro preparazione,loro impiego come supporto per la crescita in vitro di cellule epiteliali, pelli artificiali cosi' ottenute e loro impiego nei trapianti di pelle
FR2667246A1 (fr) * 1990-10-02 1992-04-03 Imedex Biomateriau a base de collagene et des applications.
US5192312A (en) * 1991-03-05 1993-03-09 Colorado State University Research Foundation Treated tissue for implantation and methods of treatment and use
CA2119064A1 (fr) * 1993-03-17 1994-09-18 Richard A. Berg Systeme d'analyse dermo-epidermique in vitro
US5891617A (en) * 1993-09-15 1999-04-06 Organogenesis Inc. Cryopreservation of harvested skin and cultured skin or cornea equivalents by slow freezing
US5518878A (en) * 1993-09-15 1996-05-21 Organogenesis Inc. Cryopreservation of cultured skin or cornea equivalents with agitation
JPH09510108A (ja) * 1994-03-14 1997-10-14 クリオライフ，インコーポレイティド 移植用処理組織及び調製方法
US5681345A (en) * 1995-03-01 1997-10-28 Scimed Life Systems, Inc. Sleeve carrying stent
US6419920B1 (en) 1995-10-25 2002-07-16 Trans Karyotic Therapies, Inc. Hybrid matrix implants and explants
US5965125A (en) 1995-10-25 1999-10-12 Transkaryotic Therapies, Inc. Hybrid matrix implants and explants
US5689961A (en) 1996-01-30 1997-11-25 Organogenesis Inc. Ice seeding apparatus for cryopreservation systems
US5827217A (en) * 1996-09-04 1998-10-27 Silver; Frederick H. Process and apparatus for harvesting tissue for processing tissue and process and apparatus for re-injecting processed tissue
US5814328A (en) * 1997-01-13 1998-09-29 Gunasekaran; Subramanian Preparation of collagen using papain and a reducing agent
WO1999046285A2 (fr) 1998-03-11 1999-09-16 University Of Southern California Procede permettant de favoriser la production d'equivalents de tissus vivants
US20060030044A1 (en) * 1998-07-13 2006-02-09 Allen-Hoffmann B Lynn Method and composition for skin grafts
ATE308610T1 (de) * 2000-05-31 2005-11-15 Fraunhofer Ges Forschung Dreidimensionales hautmodell
US20030181371A1 (en) * 2001-12-28 2003-09-25 Angiotech Pharmaceuticals, Inc. Compositions and methods of using collajolie
AUPS242702A0 (en) * 2002-05-21 2002-06-13 Colltech Australia Limited Improved method for the extraction and purification of collagen
FR2847269B1 (fr) * 2002-11-19 2006-07-28 Coletica Procede d'identification d'une modification eventuelle d'au moins un parametre biologique mettant en oeuvre des cellules vivantes jeunes et agees
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CN102119006B (zh) 2008-04-01 2017-09-26 通用医疗公司 组织移植的方法和装置
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WO2015021434A2 (fr) 2013-08-09 2015-02-12 Cytrellis Biosystems, Inc. Procédés et appareils pour le traitement de la peau à l'aide d'une ablation de tissu non thermique
US10953143B2 (en) 2013-12-19 2021-03-23 Cytrellis Biosystems, Inc. Methods and devices for manipulating subdermal fat
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6309454B1 (en) 2000-05-12 2001-10-30 Johnson & Johnson Medical Limited Freeze-dried composite materials and processes for the production thereof
EP1754513A2 (fr) 2005-08-17 2007-02-21 L'oreal Utilisation de l'acide 8-hexadécène-1,16-dicarboxylique comme agent de soin destiné à favoriser la cohésion de la couche cornée
WO2012059703A1 (fr) 2010-11-05 2012-05-10 Centre National De La Recherche Scientifique (Cnrs) Procede in vitro ou ex vivo pour la conservation et/ou la maintenance en survie d'un epiderme
WO2012163974A1 (fr) 2011-05-30 2012-12-06 L'oreal Modèle de cuir chevelu reconstruit, et traitement pour le criblage de molécules actives
WO2018020016A1 (fr) 2016-07-29 2018-02-01 L'oreal Équivalent de peau à compartiments dermiques juxtaposés distincts
WO2019063731A1 (fr) 2017-09-28 2019-04-04 L'oreal Signatures moléculaires de trois sous-populations de fibroblastes dermiques et équivalent dermique comprenant une de ces sous-populations
FR3111904A1 (fr) 2020-06-30 2021-12-31 L'oreal Bioencre pour bioimpression d’un modèle de jonction dermo-épidermique invaginée

Also Published As

Publication number Publication date
WO1986002273A1 (fr) 1986-04-24
DE3579810D1 (de) 1990-10-25
EP0197090B1 (fr) 1990-09-19
JPS62500435A (ja) 1987-02-26
US4604346A (en) 1986-08-05

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